Mechlorethamine HCl

A to Z Drug Facts

Actions An alkylating agent with cytotoxic, mutagenic, and radiomimetic actions that inhibits rapidly proliferating cells. In water or body fluids, mechlorethamine rapidly undergoes chemical transformation and reacts with various cellular compounds so the active drug is no longer present within a few minutes. Less than 0.01% of the active drug is recovered in the urine; however, more than 50% of inactive metabolites are excreted in the urine in the first 24 hr.

 Indications Hodgkin disease, lymphosarcoma, chronic myelocytic or lymphocytic leukemia, polycythemia vera, mycosis fungoides (topical), bronchogenic carcinoma; palliative treatment of malignant effusion (intrapleural, intraperitoneal, or intrapericardial use only).

 Contraindications Infectious disease; previous anaphylactic reactions to the drug.

 Route/Dosage

Lymphorsarcoma, Chronic Myelocytic or Lymphocytic Leukemia, Polycythemia Vera, Bronchogenic Carcinoma; Palliative Treatment of Malignant Effusion (Intrapleural, Intraperitoneal, or Intrapericardial Use Only)

ADULTS: IV Total dose of 0.4 mg/kg of body weight for each course (as single dose or divided doses of 0.1 to 0.2 mg/kg/day). Dose based on ideal dry body weight. May repeat courses at 3- to 6-wk intervals.

Advanced Hodgkin's Disease

ADULTS: IV When used in MOPP regimen, dose is 6 mg/m²/day on days 1 and 8 of a 28-day cycle. The dose should be decreased 50% if leukocyte count is 3000 to 3999/mm³, and 75% if the count is between 1000 and 2999/mm³ or platelets between 50,000 and 100,000/mm³. On later cycles, do not administer if leukocyte count is less than 1000/mm³ or platelets are less than 50,000/mm³.

Mycosis Fungoides

ADULTS: Topical Apply compounded solutions or ointments to the entire body surface once daily for 6 to 12 mo. If the lesions do not reappear, continue to apply every 2 to 7 days for a total of 3 yr.

Interactions None well documented.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Serious neurotoxicity including headache, hallucinations, seizures, and encephalopathy with high-dose bone marrow transplantation regimens. DERMATOLOGIC: Alopecia, hyperpigmentation, contact dermatitis with topical use. GI: Very high potential for nausea and vomiting; diarrhea, peptic ulcer, metallic taste just after drug administration. GU: Amenorrhea; sterility. HEMATOLOGIC: Bone marrow suppression, nadir at 7 to 14 days. HYPERSENSITIVITY: Anaphylactoid reaction with IV or topical administration. SPECIALSENSES: Vertigo, tinnitus; diminished hearing infrequently. OTHER: Actinic keratoses and squamous cell carcinomas with topical use; acute nonlymphocytic leukemia and non-Hodgkin lymphoma after MOPP therapy of Hodgkin disease.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy in children have not been established by well-controlled studies. Amyloidosis: Nitrogen mustard therapy may contribute to extensive and rapid development of amyloidosis; use only if foci or acute and chronic suppurative inflammation are absent. Carcinogenesis: Therapy with nitrogen mustard may be associated with an increased incidence of second malignant tumor. Chronic lymphatic leukemia: Drug toxicity, especially sensitivity to bone marrow failure, appears to be more common in chronic lymphatic leukemia than in other conditions; administer with great caution in this condition, if at all. Extravasation: Mechlorethamine is a vesicant; extravasation can cause severe local necrosis. Fertility impairment: Impaired spermatogenesis, azoospermia, and total germinal aplasia have occurred in men. GI: Nausea and vomiting usually begins 1 to 3 hr after use. Vomiting may persist for the first 8 hr, nausea for 24 hr. Hematologic: The usual course of treatment produces lymphocytopenia within 24 hr after the first injection; significant granulocytopenia occurs within 6 to 8 days and lasts for 10 days to 3 wk. Severe thrombocytopenia may lead to bleeding from the gums and GI tract, petechiae, and small SC hemorrhages. Erythrocyte and hemoglobin levels may decline, but rarely significantly, during the first 2 wk after therapy. Depression of the hematopoietic system may occur at least 50 days after starting therapy. Herpes zoster: Herpes zoster, common with lymphomas, may first appear after therapy is instituted and may be precipitated by treatment. Hypersensitivity reactions: Reactions, including anaphylaxis have occurred. Hyperuricemia: Urate precipitation may develop during therapy, particularly in the treatment of lymphomas. Intercavitary administration: Pain occurs rarely with intrapleural use; it is common with intraperitoneal injection and if often associated with nausea, vomiting, and diarrhea of 2 to 3 days duration. Transient cardiac irregularities may occur with intrapericardial injection. Tumors: Tumors of bone and nervous tissue respond poorly to therapy.

 Administration/Storage

• Store at room temperature, colder than 40°C (104°F) and protect from light and humidity.
• Mechlorethamine powder for injection should not be used if there are droplets of water in the vial before reconstitution.
• Topical preparations must be prepared in a fume hood to prevent circulation of toxic vapors into room air.
• Reconstituted solution should appear colorless. Do not use the solution if it is discolored.
• Follow procedures for proper handling and disposal of anticancer drugs. Wear gloves and avoid skin exposure and inhalation of fumes.
• Administer IV or topically.

IV

• Dilute with 10 mL of sterile water for injection or 0.9% Sodium Chloride for a concentration of 1 mg/mL. After injecting diluent into vial, with needle still in rubber stopper, shake the vial to dissolve the drug.
• IV solutions decompose rapidly; therefore, use reconstituted solutions immediately.
• Give by IV push injection or IV sidearm into a running infusion.

Topical

• Use rubber gloves to apply. Product should be used only in well-ventilated areas with chemotherapy spill kits in close proximity.
• For a topical ointment, dissolve mechlorethamine in dehydrated alcohol, filter resulting solution, and add into a petrolatum or anhydrous ointment base.
• For a topical solution, dissolve 10 mg of mechlorethamine in 50 to 60 mL of water.

 Assessment/Interventions

• Hyperuricemia may occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.
• If mechlorethamine accidentally comes into contact with skin or mucous membranes, flush with copious amounts of water, then apply a 1/6 molar solution of sodium thiosulfate to neutralize any remaining mechlorethamine. To prepare a 16% molar solution of sodium thiosulfate, dilute 4 mL of a 10% solution of sodium thiosulfate with 6 mL of sterile water, or dilute 1.6 mL of a 25% solution of sodium thiosulfate with 8.4 mL of sterile water.
• Many renal, hepatic, and bone marrow function abnormalities occur in patients with neoplastic disease who receive mechlorethamine. Check renal, hepatic, and bone marrow functions frequently.

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Advise patient, family, or caregiver that medication may be used in combination with other agents, including antiemetics, to achieve maximum benefit possible.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; fever, chills or other signs of infection; sores in mouth; unusual bleeding or bruising; pain, redness or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea or appetite loss; persistent or worsening general body weakness.
• Instruct patient to not take any prescription or otc medications or dietary supplements unless advised by health care provider.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.
• Instruct women of childbearing potential to notify health care provider if they become pregnant, plan on becoming pregnant, or are breastfeeding.
• Advise patient, family, or caregiver that following discharge frequent follow-up visits and laboratory tests will be required to monitor therapy and to be sure to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts